Controlled release pharmaceutical dosage forms are well known and provide distinct advantages for delivery of certain chemotherapies. Controlled release dosage forms are particularly useful for drugs which act optimally at certain levels of plasma concentration over extended periods of time. Controlled release systems may also avoid the presence of ineffective or toxic levels of drugs which result from periodic administration of immediate release dosage forms which provide high initial levels of drug but may leave only ineffectively small amounts of drugs in the plasma near the end of the administration periods (i.e. cycles) prior to subsequent administration of drug. Controlled release dosage forms are also desirable for providing continuous chemotherapy for chronic conditions or those with a long duration of therapy by providing drugs in a sustained released manner that only requires administration either once or twice daily instead of every four to six hours as may be indicated for a particular drug.
The administration of highly water soluble drugs in a controlled release dosage form presents particular problems. The introduction of-such highly water soluble drugs in controlled release dosage forms into a patient's digestive system has met with limited success due to the normally unpredictable leaching out of the very water soluble drug active into the digestive system when using conventional sustained release techniques. It is also challenging to provide a substantially zero or constant rate of release for drugs that are highly water soluble for extended periods of time.
It is therefore an object of the present invention to provide a multilayered controlled release pharmaceutical dosage form system, particularly for very water soluble drugs. This system provides desirable plasma levels of drugs with a substantially constant rate of release of the drugs from controlled release layers over a preselected period of time.